ArticlePharmacogenetics and genomics2014
Novel CYP2A6 variants identified in African Americans are associated with slow nicotine metabolism in vitro and in vivo.
Article in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.Biological psychiatry · 2019Pooled it
- PharmVar GeneFocus: CYP2A6.Clinical pharmacology and therapeutics · 2024Review
- Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.Clinical and translational science · 2022Article
- Transferability of Ancestry-Specific and Cross-Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations.Clinical pharmacology and therapeutics · 2021Article
- Deciphering Structural Alterations Associated with Activity Reductions of Genetic Polymorphisms in Cytochrome P450 2A6 Using Molecular Dynamics Simulations.International journal of molecular sciences · 2021Article
- Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism.Expert opinion on drug metabolism & toxicology · 2021Review
- Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Differences in the rate of nicotine metabolism among smokers with and without HIV.AIDS (London, England) · 2019Article
- Brief Report: Rate of Nicotine Metabolism and Tobacco Use Among Persons With HIV: Implications for Treatment and Research.Journal of acquired immune deficiency syndromes (1999) · 2019Article
- Lung cancer health disparities.Carcinogenesis · 2018Review
- Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences.Addiction (Abingdon, England) · 2018Article
- Precision medicine and pharmacogenetics: what does oncology have that addiction medicine does not?Addiction (Abingdon, England) · 2017Review
- CYP2A6 Genetic Variation Alters Striatal-Cingulate Circuits, Network Hubs, and Executive Processing in Smokers.Biological psychiatry · 2017Article
- Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans.Pharmacogenetics and genomics · 2017Article
- Distribution of polymorphic variants of CYP2A6 and their involvement in nicotine addiction.EXCLI journal · 2017Review
- Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Review
- Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity.Pharmacogenetics and genomics · 2016Article
- Genetic determinants of CYP2A6 activity across racial/ethnic groups with different risks of lung cancer and effect on their smoking intensity.Carcinogenesis · 2016Article
- Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.EBioMedicine · 2016Article
- CYP2A6 genotyping methods and strategies using real-time and end point PCR platforms.Pharmacogenomics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
objectiveNicotine, the main addictive ingredient in tobacco, is metabolically inactivated to cotinine primarily by the hepatic enzyme CYP2A6. Considerable genetic variation in the CYP2A6 gene results in large variation in the rates of nicotine metabolism, which in turn alters smoking behaviours (e.g. amount of cigarettes smoked, risk for dependence and success in smoking cessation). The aim of this study was to identify and characterize novel variants in CYP2A6. MATERIALS AND
methodsThe CYP2A6 gene from African American phenotypically slow nicotine metabolizers was sequenced and seven novel variants were identified [CYP2A6*39 (V68M), CYP2A6*40 (I149M), CYP2A6*41 (R265Q), CYP2A6*42 (I268T), CYP2A6*43 (T303I), CYP2A6*44 (E390K), CYP2A6*44 (L462P)]. Variants were introduced into a bi-cistronic cDNA expression construct containing CYP2A6 and P450 oxidoreductase and assessed for protein expression, enzymatic activity and stability as evaluated using western blotting and nicotine metabolism. Genotyping assays were developed and allelic frequencies were assessed in 534 African Americans.
resultsThe variants showed significantly lower protein expression (P<0.001) when compared with the wild-type as well as reduced metabolism of nicotine to cotinine when controlling for cDNA expression using P450 oxidoreductase (P<0.001). The variants also showed reduced stability at 37°C. Allelic frequencies ranged from 0.1 to 0.6% with a collective genotype frequency of 3.2%; the impact in vitro correlated significantly with in-vivo activity (R(2)=0.40-0.48, P<0.05). Together, those with a novel variant had significantly lower nicotine metabolism in vivo than those without genetic variants (P<0.01).
conclusionHere, we identified a number of novel variants with reduced/loss of CYP2A6 activity, increasing our understanding of CYP2A6 genetic variability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.